Studies of the in vitro response of human normal and tumor cells to hyperthermia alone or to hyperthermia in conjunction with x-irradiation can provide valuable information leading to clinical applications. A large number of variables, including optimum temperature, duration of treatment, and order of application with other modalities, can be investigated quickly with the normal and tumor cells in vitro. The thermal and combined thermal-radiation sensitivity of cells derived from biopsy specimens of spontaneous squamous cell carcinomas, melanomas, and fibrosarcomas will be determined, as will the response of comparable normal skin epithelial cells and kidney fibroblasts. The thermal sensitivity of tumor and comparable normal cells will be ascertained with the objective of establishing the conditions for maximum differential response. Studies of the variation in tumor and normal cell thermal responses due to such factors as pH, hypoxia, nutrient levels, and growth phase will provide additional information concerning mechanisms of cellular response. This information could aid in estimating which are the more sensitive human tumors and in designing of treatment protocols to obtain the best response.